Core B: Clinical Core Abstract: Progress in the diagnosis, treatment, and prevention of Alzheimer's Disease (AD) depends critically on the availability of large cohorts of subjects spanning the transition from normal through preclinical AD stages, mild cognitive impairment (MCI), and ultimately to early AD. The longstanding goal of the University of Pittsburgh ADRC (PITT-ADRC) Clinical Core has been to enroll these subjects, clinically characterize and longitudinally evaluate them, sample them for genetic, brain imaging, and other biomarkers, enroll them in clinical trials, and obtain their consent for the provision of autopsy tissue for further discovery. The PITT-ADRC Clinical Core has been highly successful in meeting this objective. The PITT- ADRC Clinical Core has evaluated a cohort of more than 4000 subjects since its inception, which has contributed substantially to advancement of knowledge regarding the natural history of AD, its genetic basis, the development of amyloid imaging, psychiatric comorbidities and their underlying neurobiology. During the current funding interval the Clinical Core has developed approaches to expand enrollment of individuals along the complex transition from normalcy to dementia, including Normal Control subjects, individuals with subjective cognitive decline (SCD), individuals with impaired cognitive tests (without SCD), and individuals with MCI. At present these four groups constitute nearly 40% of our annual enrollment and comprise more than 50% of our nearly 700 active subjects. These subjects provide a critical resource for many investigations in the PITT-ADRC, especially those emphasizing imaging biomarkers (including the planned Projects 1 and 2). During the current period we have maintained our strong history of neuropsychiatric characterization of all subjects and further enhanced our rate of autopsy consent, which will support the planned Project 3. Finally, we have continued are strong track record of providing genetic samples and data on large numbers of subjects annually to the Neurogenetics Core for use in local R01s and in national and international consortia. These accomplishments have prepared the PITT-ADRC Clinical Core to maintain its productivity in the following set of proposed Specific Aims: 1) To perform evaluations at study entry and at annual follow-up of Normal Control, pre-MCI, MCI, AD, and related dementia subjects participating in the PITT-ADRC; 2) To assure maximum participation in clinical, brain imaging, and autopsy studies by providing appropriate research subject referrals and clinical services during longitudinal follow-up; 3) To provide clinical data, research subjects, DNA samples, and technical and scientific leadership to support new and ongoing research projects at the PITT-ADRC, within the University of Pittsburgh, and to support national consortium studies; 4) In collaboration with the ORE Core, to facilitate recruitment of diverse participants at the earliest end of the AD spectrum into the Clinical Core, Projects 1 and 2, and ancillary studies; 5) To provide a platform of clinical evaluation, research subjects, and data to support education and training of the next generation of dementia researchers.